The goal of this small business technology transfer application is to validate and commercialize an improved means of polyp detection during colonoscopy: spectroscopic microvascular blood assessment from the endoscopically normal mucosa. Missed lesions on colonoscopy are a major problem (conservatively estimated to be ~25% of adenomas and ~4-5% of carcinomas) with devastating clinical and medico-legal consequences. While various adjuvant approaches are being developed, these lack either sensitivity or practicality for clinical medicine. Our breakthrough technology four dimensional elastic light-scattering fingerprinting (4D-ELF) allows unprecedented accuracy in sub-epithelial microvasculature analysis. Using this approach, we have reported, for the first time, that there is an early increase in blood supply (EIBS) in the histologically normal mucosa in experimental animals at risk for colon neoplasia. Thus, EIBS appeared to be an early marker of the "field carcinogenesis". This was confirmed in human colonoscopic studies using both tissue biopsies and a fiberoptic 4D-ELF probe (~400 patients). Importantly, the increased microvascular blood content was only detectable in the colonic segment (~1/3 of colon) that harbored the lesion and the magnitude mirrored the proximity to the polyp. Based on this preliminary data we hypothesize that real-time EIBS assessment will improve accuracy of neoplasia detection during colonoscopy. In phase 1 of the STTR, we propose to determine threshold (cut-off) levels of microvascular blood content (total and deoxyhemoglobin) for discrimination of colonic segments that harbor neoplasia factoring various potential EIBS modifying factors (age, gender, etc). The milestone for transition into phase 2 of the project will be the development of a highly accurate prediction rule. Phase 2 will consist of a randomized study to assess the impact of real time EIBS information on adenoma detection rate in 1600 patients. Adenoma detection rate with and without EIBS will be compared. Our conservative estimate is that EIBS guidance will improve polyp miss rate by at least a 50%. We believe that EIBS-guidance will allow the endoscopist to rapidly determine whether a colonic segment harbors neoplasia. If EIBS is negative, then rapid visual inspection is possible. Furthermore, it would aid in the relatively common scenarios such as inability to reach cecum or mucosal obscuration by residual stool. If, on the other hand, readings suggest a polyp that is not readily visualizable, then mapping the EIBS magnitude could provide precise localization. Given the clinical promise of this technologically-mature approach, we envision that this can be readily commercialized by American BioOptics through direct manufacturing/distribution of a probe-based system. Alternatively, EIBS detection could be incorporated directly into the colonoscope via parternship with an endoscope company. Most colorectal cancers, the second leading cause of cancer deaths among Americans, arise from polyps. Colonoscopy can identify and remove these polyps thus actually preventing colon cancer. However, at least a quarter of all polyps are missed on colonoscopy leading to cancer deaths and the need to perform more frequent colonoscopies. In our application, we propose to test a novel biomedical optics technology that could both greatly decrease polyp miss rate and also help speed-up the procedures. This could have major importance for colon cancer prevention efforts in the United States. [unreadable] [unreadable] [unreadable]